Behavioral Animal Model of the Emotional Response to Tinnitus and Hearing Loss

Abstract

Increased prevalence of emotional distress is associated with tinnitus and hearing loss. The underlying mechanisms of the negative emotional response to tinnitus and hearing loss remain poorly understood, and it is challenging to disentangle the emotional consequences of hearing loss from those specific to tinnitus in listeners experiencing both. We addressed these questions in laboratory rats using three common rodent anxiety screening assays: elevated plus maze, open field test, and social interaction test. Open arm activity in the elevated plus maze decreased substantially after one trial in controls, indicating its limited utility for comparing pre- and post-treatment behavior. Open field exploration and social interaction behavior were consistent across multiple sessions in control animals. Individual sound-exposed and salicylate-treated rats showed a range of phenotypes in the open field, including reduced entries into the center in some subjects and reduced locomotion overall. In rats screened for tinnitus, less locomotion was associated with higher tinnitus scores. In salicylate-treated animals, locomotion was correlated with age. Sound-exposed and salicylate-treated rats also showed reduced social interaction. These results suggest that open field exploratory activity is a selective measure for identifying tinnitus distress in individual animals, whereas social interaction reflects the general effects of hearing loss. This animal model will facilitate future studies of the structural and functional changes in the brain pathways underlying emotional distress associated with hearing dysfunction, as well as development of novel interventions to ameliorate or prevent negative emotional responses.

Keywords: anxiety; depression; distress; hearing loss; salicylate; sound exposure; tinnitus.

Fig. 1

Elevated plus-maze activity in the open arms decreases when measured across repeated test sessions (T1, T2, T3) in control rats. Percent entries (a), percent time spent (b), and percent distance traveled in the open arms (c) were highest in T1 for all but two rats, which showed no open arm activity in T1. Locomotor activity indicated by total number of open plus closed arm entries (d), total time spent in arms (e), and total distance traveled in arms (f) were constant or increased slightly across test sessions. Data are shown for individual subjects (open symbols) and the average across subjects (thick line). Different symbol shapes correspond to different individual rats

Fig. 2

Open field behavior is consistent across multiple test sessions in control rats. Percent center entries (a), percent time spent in the center (b), percent distance traveled in the center (c), and total distance traveled (d) are shown for individual subjects (open symbols) and the average across subjects (thick line). Different symbol shapes correspond to different individual rats

Fig. 3

Open field behavior measured across test sessions in rats prior (Pre1, Pre2) to and after (Post1, Post2) damaging monaural sound exposure revealed a range of anxiety phenotypes. Percent center entries were low in some rats prior to or after sound exposure (a). Percent time spent in the center was reduced overall (b), percent distance traveled in the center was unchanged (c), and total distance traveled was reduced overall (d) after sound exposure. Data are shown for individual subjects screened for tinnitus (red symbols) and not screened for tinnitus (black symbols). The gray area in a highlights subjects with extremely high-anxiety phenotypes. Different symbol shapes correspond to different individual rats

Fig. 4

Open field behavior measured in one test session in a second cohort of control rats (open black symbols) and in monaurally sound-exposed rats (filled gray symbols) is consistent with results from the first cohorts. Percent entries into the center (a), percent time spent in center (a), percent distance traveled in center (c), and total distance traveled (d) are shown for individual subjects. Different symbol shapes correspond to different individual rats

Fig. 5

Open field behavior measured across test sessions in rats prior to (Pre1), during (SS/saline1, SS/saline2), and after (Post1, Post2) injections of 100 to 300 mg/kg sodium salicylate (SS) (blue symbols) or saline (black symbols). Squares—rats tested with 200 mg/kg and again with 100 mg/kg salicylate; triangles—300 mg/kg; inverted triangles—250 mg/kg; diamonds—200 mg/kg; circles—saline. All three rats tested with 100 mg/kg salicylate showed no center entries; therefore, the points overlap and appear as one symbol in (a–c). Percent entries into the center were reduced in some rats during treatment (a). Percent time spent in center was reduced overall (b), percent distance traveled in center was reduced in some rats (c), and total distance traveled was reduced overall (d) during treatment. Data are shown for individual subjects. Different symbol shapes correspond to different individual rats

Fig. 6

The number of social interactions was consistent measured across repeated test sessions in control rats (a). Social interactions decreased after sound exposure compared to pre-exposure test sessions (b). Red symbols in b indicate animals previously screened for tinnitus, and black symbols indicate animals not screened for tinnitus. Social interactions were also decreased in a second cohort of sound-exposed rats (filled gray symbols) compared to a second cohort of controls (open black symbols) (c). Sodium salicylate-treated rats (blue symbols) also showed reduced social interaction compared to before treatment (d). Different symbol shapes correspond to different individual rats